Prevalence and predictive value of sarcopenia in hospitalized patients with ischemic colitis

Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration.


Study population
We retrospectively reviewed hospitalized patients who had been diagnosed with IC at Keimyung University Dongsan Medical Center between January 2007 and February 2022.The inclusion criteria were: IC confirmed by colonoscopy or sigmoidoscopy and assessed by contrast-enhanced abdominopelvic computed tomography (CT) at presentation, or treated by surgery for complications of severe IC.The exclusion criteria comprised no inpatient treatment, IC diagnosed while in hospital for other illnesses, concomitant infectious colitis with the etiology proven by stool tests, previous or current colorectal cancer, history of colectomy, or missing clinical data or abdominopelvic CT images covering the third lumbar vertebra (L3) area.The Institutional Review Board (IRB) of Keimyung University Dongsan Hospital approved the study (Approval no: 2023-09-038) which proceeded according to the ethical principles enshrined in the Declaration of Helsinki (2013 amendment).The IRB of Keimyung University Dongsan Hospital waived the need for informed consent owing to the retrospective nature of the study.

Data collection and CT protocol
The demographics of the patients, laboratory data, endoscopic and abdominopelvic CT findings, and histological results were extracted from the electronic medical records.The clinical data comprised body mass index (BMI), the American Society of Anesthesiologists (ASA) classification score, blood pressure, heart rate, body temperature, and presence or absence of abdominal rebound tenderness.Comorbidities were classified using the Charlson comorbidity index (CCI) 19 .
Abdominopelvic CT images were routinely acquired using 64-or 128-channel multidetector CT scanners (Siemens Medical Solutions Inc., Malvern, PA, USA; GE HealthCare Technologies Inc., Chicago, IL, USA) at 100-120 kVp using automatic exposure control.Portal venous phase scans typically occurred at 70 s after an intravenous injection of an iodinated contrast agent.All images were reconstructed as 5-mm slice thickness without interslice gaps.A trained observer (BCA) reviewed the CT images and reports of IC to determine affected segments, bowel wall thickening or edema, pericolic infiltration, decreased contrast enhancement, and intramural pneumatosis 20 .Radiologists then reviewed discordant findings between the CT imaging data and reports to confirm involved lesions.Endoscopic findings of inflamed areas such as mucosal redness, erosion, and ulcer were also reviewed 21 .Ulcers were defined as "deep" when the depth the most inflamed area was > 3 mm.The left colon was defined as rectum, sigmoid colon, and the splenic flexure.The right colon was defined as the cecum, ascending colon, and hepatic flexure.The involvement of two segments was defined as IC found in any two of the left, transverse, and right colon.We also reviewed histopathologic findings, which are rarely diagnostic 9 , but IC was primarily diagnosed based on combined clinical, imaging, and endoscopic or surgical findings.

Definition of sarcopenia
Skeletal muscle area (SMA), total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and bilateral psoas muscle areas were calculated from abdominopelvic CT images acquired at the L3 level using AsanJ-Morphometry™ software (Fig. 1) 22 .Skeletal muscle indices were defined as the total cross-sectional area of skeletal muscle at the L3 level divided by the BMI (SMA/BMI) or height squared (SMA/height 2 ).The sex-specific cutoff values of SMA/BMI and SMA/height 2 for defining sarcopenia were 4.97 and 3.46 cm 2 /m 2 in men, and 39.8 and 28.4 cm 2 /m 2 in women with reference to the results of a recent Asian population study 23 .

Severity of IC
The severity of IC was evaluated according to the American College of Gastroenterology clinical guidelines 1 .Mild IC was defined as symptomatic segmental colitis not solely in the right colon without the risk factors for moderate IC listed below.Moderate IC was confirmed when up to any three of the following criteria were met: Figure 1.Computed tomography (CT) images of the skeletal muscle area (SMA, shown in bright purple) were obtained at the level of L3 vertebrae in sarcopenic (A) and non-sarcopenic (B) ischemic colitis patients using the "AsanJ-Morphometry" software 22 .

Statistical analysis
Categorical variables are expressed as numbers and percentages and were analyzed using chi-square or Fisher exact tests.Continuous variables are expressed as medians (interquartile range [IQR]) and were analyzed using Student t-tests or Wilcoxon rank sum tests depending on the distribution of variables.We identified predictors of mortality or the need for surgical intervention using Firth penalized-likelihood logistic regression to minimize analytical bias caused by the rarity of the event and complete separation 24 .Variables with P < 0.1 in the univariable analysis were further assessed using multivariable backward elimination.Values with two-sided P < 0.05 were considered statistically significant.All data were statistically analyzed using R version 4.2.3 (RStudio, Inc., Boston, MA, USA).

Body composition measures at the third lumbar (L3) vertebra
The values for SMI/BMI, and SMA/height 2 were significantly lower in male and female patients with severe, than mild-to-moderate IC (Table 2).The prevalence of sarcopenia defined as SMI/BMI was higher in in males (72.2%   www.nature.com/scientificreports/

Discussion
We investigated associations between sarcopenia and IC, and the prognostic value of sarcopenia.The prevalence of sarcopenia in hospitalized patients with IC differed according to whether it was defined as SMA/BMI (49.3%) or SMA/height 2 (34.7%).About 50% of the patients with sarcopenia had severe IC and 33% presented with deep ulcers.The prognosis of patients with sarcopenia was worse in terms of IC.Moreover, sarcopenia was identified as an independent predictor of mortality or surgical intervention.To our knowledge, this is the first study to determine an association between IC and sarcopenia.Sarcopenia can be caused by infrequent skeletal muscle use, malnutrition, endocrine and metabolic changes, chronic inflammation, and consumptive disorder 25 .The prevalence of sarcopenia is relatively high among patients with stroke (42%), inflammatory bowel disease (41.6%), cancer (38.6%), liver cirrhosis (37.5%), heart failure (34%), rheumatoid arthritis (30.2%), end-stage renal disease (28.5%), chronic obstructive pulmonary disease (21.6%), chronic pancreatitis (17%-62%), and type 2 diabetes (18%) 26 .We found here that sarcopenia is prevalent among hospitalized patients with IC, and that this tendency was more pronounced among those with severe IC.
Although the mechanisms underlying sarcopenia in IC require further investigation, we believe that shared risk factors associated with older age and comorbidities could explain the association between IC and sarcopenia 27,28 .Chronic inflammation, nutritional deficiency, lack of exercise, and dysbiotic gut microbiota in patients with inflammatory bowel disease 29 , might also contribute to the development of sarcopenia in IC.In particular, the intestinal microbiota is influenced not only by the aging process but also by several chronic diseases that interact reciprocally with intestinal ischemia according to preclinical animal studies 30,31 .Furthermore, the intestinal microbiota influences muscle function and quality through the gut-muscle axis in humans and experimental animals 26,32,33 .Appropriately-designed prospective studies are warranted to validate the relationship between IC and sarcopenia and identify the underlying mechanisms.
Sarcopenia can lead to impaired physical function, a diminished quality of life, increased risk of complications, and increased short-and long-term mortality 27,34,35 .The present findings also indicated that sarcopenia can predict a poor prognosis in patients with IC.This finding was in line with the established predictors, peritoneal signs, LDH > 450 U/L, bilateral or right-sided distribution, hepatitis C positivity, male sex, and chronic kidney disease 9 .This implies that patients with sarcopenia and IC are at a higher risk of treatment failure with conservative management, underscoring the importance of careful monitoring and proactive treatment approaches.This study has some limitations.Firstly, we defined sarcopenia based on L3 CT images because most hospitalized patients with IC at our institution had been evaluated by CT.This method is valuable because muscle can be readily quantified from other body components.However, it's worth noting the absence of a gold standard for diagnosing sarcopenia 36 .We acknowledge that the lack of measurement of skeletal muscle using dual energy X-ray absorptiometry, magnetic resonance imaging, and electrical bioimpedance, or functional indices, such as physical strength and frailty, might hinder the interpretation and generalization of our findings.Secondly, cutoff values for sarcopenia vary across studies and populations 37,38 .We addressed this issue by referring to a recently published study of a large Asian population in which the cutoff point for sarcopenia was defined as a T-score < 2.0 23 .In that study, SMA/BMI was proposed as the most reliable CT index for reflecting age-related muscle changes and achieving a high diagnostic yield 23 .Thirdly, our study population did not include patients with IC who were not admitted to hospital, which might limit the generalizability of our findings.However, IC is usually a milder disease that responds well to conservative management when hospitalization is not required.Therefore, the clinical implications of identifying sarcopenia in this group might not be as significant.Finally, since we included patients with IC who underwent endoscopy and CT, we might have excluded some patients with severe IC who did not undergo endoscopy owing to unstable vital signs, peritoneal signs, and ominous radiologic findings.However, to mitigate the risk of excluding those patients, we also included patients with severe IC that was surgically treated without endoscopic evaluation and whose diagnoses were further confirmed by clinical, imaging, and surgical pathology findings.
In conclusion, we found that the prevalence of sarcopenia is higher in hospitalized patients with, than without IC.We also uncovered a significant association between sarcopenia and IC severity, with sarcopenia being an independent predictor of mortality or surgical intervention.These findings suggest the need for meticulous monitoring, prompt medical treatment, and timely surgical consultation, particularly for patients with IC and sarcopenia.

Figure 2 .
Figure 2. Flow chart of patient inclusion and exclusion.CT computed tomography.

Table 1 .
Clinical characteristics of the study population.a Forty-one patients with a history of abdominal surgery (appendectomy, n = 16; gynecologic surgery, n = 12; cholecystectomy, n = 3; vascular surgery, n = 3; peritonitis surgery, n = 2; Cesarean section, n = 1, exploratory laparotomy, n = 1; liver segmentectomy, n = 1; cecectomy, n = 1).b Tachycardia is defined as heart rate > 100 beats/min.c Hypotension is defined as a systolic blood pressure < 90 mmHg.d We identified 30 patients without definite IC involvement on CT images but were diagnosed by endoscopy.The distribution of IC was as follows: right colon, n = 4; transverse colon, n = 1; left colon, n = 22; involvement of 2 segments, n = 3. ASA American Society of Anesthesiologists, BMI body mass index, BUN blood urea nitrogen, CRP C-reactive protein, CT computed tomography, IC ischemic colitis, IQR interquartile range, LDH lactate dehydrogenase, SMA skeletal muscle area, TPN total parenteral nutrition, WBC white blood cells.

Table 2 .
Comparison of body composition characteristics at L3 vertebra between patients with mild-tomoderate and severe ischemic colitis according to sex.BMI body mass index, IC ischemic colitis, SMA skeletal muscle area.

Table 4 .
Univariable and multivariable Firth's penalized logistic regression analysis for predicting mortality or surgical intervention.a Multivariable analysis was conducted by incorporating SMA/BMI.b Multivariable analysis was conducted by incorporating SMA/height 2 .ASA The American Society of Anesthesiologists, BMI body mass index, BUN blood urea nitrogen, CI confidence interval, CRP C-reactive protein, LDH lactate dehydrogenase, OR odds ratio, SMA skeletal muscle area, WBC white blood cell.